Effectiveness of Amantadine Hydrochloride for Treatment of Severe Traumatic Brain Injury (TBI)

NCT00970944 | Completed Phase 2 Results DMC

• 1 other identifier: H133A031713
• Study Type: interventional
• Target: 184
• Locations: 3 countries
• Sites: 11

Brief Summary

This is a controlled trial of amantadine to improve level of function following severe traumatic brain injury. The purpose of this study is:

1. 1.To determine whether amantadine hydrochloride, given in a dose of 200-400 mg, improves functional recovery from the vegetative and minimally conscious states
2. 2.To determine whether amantadine-related gains in function persist following drug discontinuation
3. 3.To determine the safety profile of amantadine in patients with disorders of consciousness

Conditions

Traumatic Brain Injury

Keywords

Traumatic Brain Injury; Rehabilitation; Disorders of Consciousness; Functional Outcome; Amantadine Hydrochloride

Outcome Measures

Primary Outcomes (1)

• Disability Rating Scale: Functional Status

  Measure of function after traumatic brain injury (TBI) intended to measure function from "coma to community." Minimum score= 0; Maximum score= 29 (High scores are indicative of greater degree of disability).

  Randomization and weekly for 6 weeks. The primary study endpoint was week 4 and drug washout was week 6.

Secondary Outcomes (1)

• JFK Coma Recovery Scale-Revised: Neurobehavioral Status

  Week 4 (primary endpoint); Week 6 (post-washout)

Study Arms (2)

Amantadine HCL

EXPERIMENTAL

100mg BID administered for 2 weeks, then increased to 150mg BID in week 3 if change on primary outcome measure (ie Disability Rating Scale, DRS) was less than 2 points after week 2. If change in DRS score remained less than 2 points after week 3, dose was increased to 200mg BID in week 4.

Drug: Amantadine Hydrochloride

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Amantadine Hydrochloride DRUG

184 patients who remain in VS or MCS 4 - 16 weeks post-TBI will be randomized in a stratified fashion to 4 weeks of amantadine (200 - 400 mg/day) followed by a 2-week washout period. The Disability Rating Scale (DRS) will be the primary dependent variable with the Coma Recovery Scale-Revised (CRS-R) serving as a supplementary measure.

Also known as: Symmetrel

Amantadine HCL

Placebo DRUG

Placebo administered twice daily.

Placebo

Eligibility Criteria

• Age: 16 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Individuals between ages 16 and 65 with traumatic brain injury as defined by the TBI Model System syllabus (i.e., damage to brain tissue caused by an external mechanical force as evidenced by loss of consciousness or post-traumatic amnesia due to brain trauma, skull fracture, or objective neurological findings that can be reasonably attributed to TBI on physical or mental status examination).
• Individuals are at least 4 weeks but less than 16 weeks post-injury and have a Disability Rating Scale (DRS) score at enrollment of 12 or greater, and no consistent command following or functional communication (as defined by the JFK.

You may not qualify if:

• Women who are pregnant,
• Individuals with missile-type penetrating brain injury,
• Premorbid major CNS/developmental abnormality (e.g., mental retardation, prior significant brain damage, etc.),
• History of more than 1 seizure (clinical or electrographic, but not including epileptiform or other irritative discharges) in the 4 weeks prior to enrollment (individuals with premorbid idiopathic epilepsy are eligible to enroll under two conditions: a) if their pre-injury seizure frequency was less than once/month and they have had no more than 1 seizure/month since injury and b) if a clear provocation was present that would otherwise disqualify a subject, the subject can be enrolled, since these events would not be considered idiopathic),
• Prior exposure to AH post-TBI,
• Unwillingness to discontinue or change confounding psychotropic drugs prior to enrollment, OR
• Allergy or medical contraindication to AH and significant impairment of renal function (as evidenced by a calculated creatinine clearance of \< 60 ml/min).

Sponsors & Collaborators

• JFK Medical Center: lead
• U.S. Department of Education: collaborator

Study Sites (11)

Braintree Rehabilitation Hospital

Braintree, Massachusetts, 02184, United States

Location

Methodist Rehabilitation Center

Jackson, Mississippi, 39216, United States

Location

Columbia University

New York, New York, 10032, United States

Location

Sunnyview Rehabilitation Hospital

Schenectady, New York, 12308, United States

Location

Charlotte Rehabilitation Center

Charlotte, North Carolina, 28203, United States

Location

Moss Rehabilitation Research Institute

Elkins Park, Pennsylvania, 19027, United States

Location

Bryn Mawr Rehabilitation Hospital

Malvern, Pennsylvania, 19355, United States

Location

Texas NeuroRehabilitation Center

Austin, Texas, 78745, United States

Location

Hvidovre University Hospital

Hvidovre, DK 2650, Denmark

Location

Neurologische Klinik Bad Aibling

Bad Aibling, 83043, Germany

Location

Fachkrankenhaus Neresheim

Neresheim, 73450, Germany

Location

Related Publications (1)

• Giacino JT, Whyte J, Bagiella E, Kalmar K, Childs N, Khademi A, Eifert B, Long D, Katz DI, Cho S, Yablon SA, Luther M, Hammond FM, Nordenbo A, Novak P, Mercer W, Maurer-Karattup P, Sherer M. Placebo-controlled trial of amantadine for severe traumatic brain injury. N Engl J Med. 2012 Mar 1;366(9):819-26. doi: 10.1056/NEJMoa1102609.

  PMID: 22375973 DERIVED

MeSH Terms

Conditions

Brain Injuries, Traumatic; Consciousness Disorders

Interventions

Amantadine

Condition Hierarchy (Ancestors)

Brain Injuries; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Craniocerebral Trauma; Trauma, Nervous System; Wounds and Injuries; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Adamantane; Bridged-Ring Compounds; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals

Results Point of Contact

• Title: Joseph T Giacino, PhD
• Organization: Spaulding Rehabilitation Hospital

jgiacino@partners.org

617-573-2757

Study Officials

• Joseph T. Giacino, Ph.D.

  Spaulding Rehabilitation Hospital

  PRINCIPAL INVESTIGATOR

• John Whyte, MD, Ph.D.

  Moss Rehabilitation Research Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Director of Rehabilitation Neuropsychology

Study Record Dates

• First Submitted: September 2, 2009
• First Posted: September 3, 2009
• Study Start: February 1, 2003
• Primary Completion: March 1, 2010
• Study Completion: March 1, 2010
• Last Updated: September 24, 2012
• Results First Posted: September 24, 2012

Record last verified: 2012-09

Locations

US (8); DK (1); DE (2)